The relation of the immune response to the genetic basis of natural resistance to Trypanosoma cruzi in the mouse is to be studied. Purified populations of cells from an unimmunized resistant mouse strain will be transferred to mice of a susceptible strain to see which cells of the immune system are capable of augmenting resistance. The homoral and cellular immune responses of resistant and susceptible mouse strains will be compared by newly developed methods. A genetic analysis of natural resistance will determine the number of genes governing resistance and their linkage to other known traits. Possible immune mechanisms important to parasite elimination in natural resistance and acquired resistance will evaluated. The roles of humoral immunity and cellular immunity will be studied by specific depletion of cell populations in resistant mice, by transfer of fractionated immune spleen cells to susceptible mice, and by transfer of passive antibody. A vaccine will be developed using drug-treated trypomastigotes to produce a live, nonreplicating parasite which will combine the immuno-genicity of a live vaccine with the safety of a dead vaccine.